Brain serotonin synthesis capacity in obsessive-compulsive disorder: effects of cognitive behavioral therapy and sertraline

Lissemore, Jennifer I.; Sookman, Debbie; Gravel, Paul; Berney, Alexandre; Barsoum, Amir; Dikšić, Mirko; Nordahl, Thomas E.; Pinard, Gilbert; Sibon, Igor; Cottraux, Jean; Leyton, Marco; Benkelfat, Chawki

doi:10.1038/s41398-018-0128-4

Cited by 48 publications

(26 citation statements)

References 63 publications

(73 reference statements)

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“…After sertraline Neurosurgery treatment, in treatment responders and partial responders, serotonin synthesis capacity increased brain-wide. 25 This change was correlated with Y-BOCS reduction.…”

Section: Pharmacotherapymentioning

confidence: 88%

Defining functional brain networks underlying obsessive–compulsive disorder (OCD) using treatment-induced neuroimaging changes: a systematic review of the literature

Bijanki

Pathak

Najera

et al. 2021

J Neurol Neurosurg Psychiatry

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Approximately 2%–3% of the population suffers from obsessive–compulsive disorder (OCD). Several brain regions have been implicated in the pathophysiology of OCD, but their various contributions remain unclear. We examined changes in structural and functional neuroimaging before and after a variety of therapeutic interventions as an index into identifying the underlying networks involved. We identified 64 studies from 1990 to 2020 comparing pretreatment and post-treatment imaging of patients with OCD, including metabolic and perfusion, neurochemical, structural, functional and connectivity-based modalities. Treatment class included pharmacotherapy, cognitive–behavioural therapy/exposure and response prevention, stereotactic lesions, deep brain stimulation and transcranial magnetic stimulation. Changes in several brain regions are consistent and correspond with treatment response despite the heterogeneity in treatments and neuroimaging modalities. Most notable are decreases in metabolism and perfusion of the caudate, anterior cingulate cortex, thalamus and regions of prefrontal cortex (PFC) including the orbitofrontal cortex (OFC), dorsolateral PFC (DLPFC), ventromedial PFC (VMPFC) and ventrolateral PFC (VLPFC). Modulating activity within regions of the cortico-striato-thalamo-cortical system may be a common therapeutic mechanism across treatments. We identify future needs and current knowledge gaps that can be mitigated by implementing integrative methods. Future studies should incorporate a systematic, analytical approach to testing objective correlates of treatment response to better understand neurophysiological mechanisms of dysfunction.

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Section: Pharmacotherapymentioning

confidence: 88%

Defining functional brain networks underlying obsessive–compulsive disorder (OCD) using treatment-induced neuroimaging changes: a systematic review of the literature

Bijanki

Pathak

Najera

et al. 2021

J Neurol Neurosurg Psychiatry

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“…57 In clinical studies, selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy were found to increase serotonin synthesis capability in widespread areas of the brain; further, increased serotonin synthesis in the raphe nucleus was associated with clinical improvement. 58 SSRIs are the most effective medical treatment available for OCD, and dopamine antagonists have been used in some treatment-refractory cases. 59,60 More recently, abnormalities of glutamate transmission have also been described in OCD patients.…”

Section: Obsessive-compulsive Disordermentioning

confidence: 99%

Clinical applications of neurochemical and electrophysiological measurements for closed-loop neurostimulation

Price¹,

Rusheen

Barath³

et al. 2020

Neurosurgical Focus

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The development of closed-loop deep brain stimulation (DBS) systems represents a significant opportunity for innovation in the clinical application of neurostimulation therapies. Despite the highly dynamic nature of neurological diseases, open-loop DBS applications are incapable of modifying parameters in real time to react to fluctuations in disease states. Thus, current practice for the designation of stimulation parameters, such as duration, amplitude, and pulse frequency, is an algorithmic process. Ideal stimulation parameters are highly individualized and must reflect both the specific disease presentation and the unique pathophysiology presented by the individual. Stimulation parameters currently require a lengthy trial-and-error process to achieve the maximal therapeutic effect and can only be modified during clinical visits. The major impediment to the development of automated, adaptive closed-loop systems involves the selection of highly specific disease-related biomarkers to provide feedback for the stimulation platform. This review explores the disease relevance of neurochemical and electrophysiological biomarkers for the development of closed-loop neurostimulation technologies. Electrophysiological biomarkers, such as local field potentials, have been used to monitor disease states. Real-time measurement of neurochemical substances may be similarly useful for disease characterization. Thus, the introduction of measurable neurochemical analytes has significantly expanded biomarker options for feedback-sensitive neuromodulation systems. The potential use of biomarker monitoring to advance neurostimulation approaches for treatment of Parkinson’s disease, essential tremor, epilepsy, Tourette syndrome, obsessive-compulsive disorder, chronic pain, and depression is examined. Further, challenges and advances in the development of closed-loop neurostimulation technology are reviewed, as well as opportunities for next-generation closed-loop platforms.

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“…OCD, which shares many similarities with eating disorders, has been associated with gut microbiome dysregulation (Turna et al, 2017) and altered serotonin activity in the brain (Lissemore et al, 2018). Just like eating disorders, OCD is associated with high comorbidity with other mental disorders (Hofmeijer-Sevink et al, 2013).…”

Section: Comorbidity Of Eating Disordersmentioning

confidence: 99%

Eating Disorders: An Evolutionary Psychoneuroimmunological Approach

et al. 2019

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Eating disorders are evolutionarily novel conditions. They lead to some of the highest mortality rates of all psychiatric disorders. Several evolutionary hypotheses have been proposed for eating disorders, but only the intrasexual competition hypothesis is extensively supported by evidence. We present the mismatch hypothesis as a necessary extension to the current theoretical framework of eating disorders. This hypothesis explains the evolutionarily novel adaptive metaproblem that has arisen when mating motives conflict with the large-scale and easy availability of hyper-rewarding but obesogenic foods. This situation is exacerbated particularly in those contemporary environments that are characterized by sedentary lifestyles, ever-present junk foods, caloric surplus and the ubiquity of social comparisons that take place via social media. Our psychoneuroimmunological model connects ultimate-level causation with proximate mechanisms by showing how the adaptive metaproblem between mating motives and food rewards leads to chronic stress and, further, to disordered eating. Chronic stress causes neuroinflammation, which increases susceptibility to OCD-like behaviors that typically co-occur with eating disorders. Chronic stress upregulates the serotonergic system and causes dysphoric mood in anorexia nervosa patients. Dieting, however, reduces serotonin levels and dysphoric mood, leading to a vicious serotonergic-homeostatic stress/starvation cycle whereby cortisol and neuroinflammation increase through stringent dieting. Our psychoneuroimmunological model indicates that between-individual and within-individual variation in eating disorders partially arises from (co)variation in gut microbiota and stress responsivity, which influence neuroinflammation and the serotonergic system. We review the advances that have been made in recent years in understanding how to best treat eating disorders, outlining directions for future clinical research. Current evidence indicates that eating disorder treatments should aim to reduce the chronic stress, neuroinflammation, stress responsivity and gut dysbiosis that fuel the disorders. Connecting ultimate causes with proximate mechanisms and treating biopsychosocial causes rather than manifest symptoms is expected to bring more effective and sophisticated long-term interventions for the millions of people who suffer from eating disorders.

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Brain serotonin synthesis capacity in obsessive-compulsive disorder: effects of cognitive behavioral therapy and sertraline

Cited by 48 publications

References 63 publications

Defining functional brain networks underlying obsessive–compulsive disorder (OCD) using treatment-induced neuroimaging changes: a systematic review of the literature

Defining functional brain networks underlying obsessive–compulsive disorder (OCD) using treatment-induced neuroimaging changes: a systematic review of the literature

Clinical applications of neurochemical and electrophysiological measurements for closed-loop neurostimulation

Eating Disorders: An Evolutionary Psychoneuroimmunological Approach

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